The long-term goal of this application is to study the antiviral, biochemical, and pharmacological profiles of new b-D- and b-L chiral nucleosides. The specific aims of the current application are concerned with these studies on b-D-2',3'-didehydro-2',3'-dideoxy-5-fluorocytidine (D-D4FC) and the related class of D-2',3'-didehydro-2',3'-dideoxy-2'-fluoronucleosides (D-2'-F-d4Ns). Both in vitro and in vivo investigations are proposed. The rationale for the choice of these compounds for the studies proposed is based on the observation of the discovery that certain 2',3'-didehydro-2',3'-dideoxynucleosides (d4N) and their 2'-fluoro analogs are antiviral agents that possess selective activity against the M184V HIV-1 variants, that lack cross-resistance with some known antiviral agents, and that have dual antiviral activity against HIV-1 and HBV.